Soluble L-Selectin (sCD62L) Umbilical Cord Plasma Levels Increase with Gestational Age

Abstract

L-Selectin (CD62L) is a leukocyte surface membrane glycoprotein involved in extravasation and homotypic aggregation which is rapidly cleaved off after cellular activation. From culture supernatants and body fluids, soluble L-selectin (sCD62L) has been recovered with its functional activity retained. We devised a sensitive enzyme-linked immunoassay for quantitation of sCD62L which was used to measure sCD62L in umbilical cord plasma of 255 human newborns with a gestational age (GA) of 23-43 wk (median 38 wk). sCD62L levels ranged from 1.14-13.8 pmol/mL (median 7.2 pmol/mL) and showed strong correlations with GA (r = 0.71, p < 0.001), birth weight (r = 0.66, p < 0.001), and absolute neutrophil cell counts (ANC) (r = 0.62, p < 0.001) obtained from a peripheral vein within the first 6 h of life (n = 153), whereas there was a weak inverse correlation with absolute normoblast counts (r = -0.27, p < 0.001). In multiple regression analysis, only GA and ANC retained a significant association with sCD62L levels (p < 0.001). Decreased sCD62L levels were found to be associated with multiple gestation (4.8 +/- 2.4 pmol/mL versus 7.7 +/- 2.3 pmol/mL, p < 0.05) also when considering GA and ANC as covariates. In contrast, increased sCD62L levels in infants born from meconium-stained amniotic fluid, and decreased levels in newborns with acute bacterial infection could be fully attributed to differences in GA and ANC.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding of human serum amyloid P componentto L‐selectin

“…SAP is a major constituent of amyloid deposits, which is related to its marked resistance to proteolysis [23] apparently conferred to SAP-bound proteins [28]. We assume that the unexpectedly high levels of circulating L-selectin in humans [9,12] and its long half-life [13] may be linked to protection from degradation conferred to soluble L-selectin by SAP.…”

“…All three bands were identified as SAP or SAP split products by mass spectroscopy sequencing. However, the Sepharose matrix itself binds SAP in a Ca 2+ -dependent fashion [16][17][18], which readily becomes relevant as SAP concentrations in human plasma [19,20] exceed those of soluble L-selectin [9,12]. SAP was also eluted from human plasma-loaded Sepharose control columns upon Ca 2+ chelation by EDTA, and commercially obtained SAP bound almost equally well to asialofetuin-coupled Sepharose as to Sepharose coupled to recombinant Lselectin.…”

“…Thus, while both GlyCAM-1 and soluble L-selectin have the capability to negatively affect leukocyte migration, they appear to mutually neutralize their inhibitory activity. As SAP concentrations in human plasma [19,20] exceed those of soluble L-selectin [9,12], SAP may act as a sink for soluble L-selectin. So far, none of the numerous reports on soluble L-selectin plasma concentrations in various clinical settings has discriminated between free and bound soluble Lselectin, and SAP may modulate the functional consequences of altered circulating L-selectin concentrations.…”

“…On a molar basis, L-selectin serum concentrations exceed those of other soluble adhesion molecules by one to two orders of magnitude. With an average density of 10 4 -10 5 surface-expressed Lselectin molecules per leukocyte [10,11] and L-selectin serum concentrations of 10-12 nmol/L (6-7 Â 10 15 molecules/L) [12], it can be calculated that the number of soluble L-selectin molecules present in a given volume of blood exceeds that of L-selectin molecules expressed on the surface of the leukocytes in the same sample.…”

Immunological peculiarities of extremely preterm infants: a challenge for the prevention of nosocomial sepsis

“…A P-selectina das plaquetas e células endoteliais é expressa de forma bastante tênue pelo endotélio fetal antes da 27ª semana de gestação, e sua expressão é praticamente normal no recém-nascido a termo e diminuída no recém-nascido pré-termo 22 . A L-selectina é expressa essencialmente nos leucócitos, havendo baixos níveis no cordão de recém-nascidos, principalmente em recém-nascidos pré-termo 23,24 . Durante o primeiro mês de vida, a expressão de L-selectina é reduzida nas células de neonatos, quando comparadas com as células de adultos 25 .…”